2005: Characterization of in vivo expanded OspA-specific human T-cell clones.

1: Clin Immunol. 2005 Jun;115(3):313-22. Links


Characterization of in vivo expanded OspA-specific human T-cell clones.

Ausubel LJ, O'connor KC, Baecher-Allen C, Trollmo C, Kessler B, Hekking
B, Merritt D, Meyer AL, Kwok B, Ploegh H, Huber BT, Hafler DA.

Laboratory of Molecular Immunology, Center for Neurologic Diseases,
Brigham and Women's Hospital and Harvard Medical School, 77 Avenue
Louis Pasteur, Boston, MA 02115, USA.

A panel of CD4 T-cell clones was isolated from synovial fluid by single
cell flow cytometry from a patient with treatment-resistant Lyme
arthritis using a DRB1*0401 major histocompatibility complex (MHC)
class II tetramer covalently loaded with outer surface protein A (OspA)
peptide164-175, an immunodominant epitope of Borrelia burgdorferi.
Sequencing of the T-cell receptors of the OspA reactive clones showed
significant skewing of the T-cell receptor repertoire. Of the 101
T-cell clones sequenced, 81 possessed TCR beta chains that were present
in at least one other clone isolated. Complete sequencing of both alpha
and beta chains of a subset of clones showed that at least two distinct
T-cell clones were expanded in vivo. Binding studies using a panel of
Ala-substituted peptide ligands were performed to determine potential
MHC binding sites of the OspAp164-175 to DRB1*0401. In addition, T-cell
clones were tested functionally for their reactivity to the wild-type
peptide as well as to altered peptide ligands (APLs) and peptide
libraries based on the OspA epitope in order to determine the TCR
contact residues and the stringency in T cell recognition. We are among
the first to define the characteristics of TCR usage of T cells
isolated from an inflamed immune compartment in an individual with an
autoimmune disease potentially triggered by a microbial antigen.

PMID: 15893699 [PubMed - in process]

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